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Motoring to a signaling check-up

Smad2 (green) motors along microtubules (red). HILL/ELSEVIER

The Smad2 signaling protein is shuttled back to the membrane to check up on its receptor, according to Julie Batut, Michael Howell and Caroline Hill (Cancer Research UK, London). The check-ups ensure that intracellular signaling accurately reflects the activation status of the membrane-bound receptor.

Smad proteins are phosphorylated by and act downstream of TGF-ß receptors. Once Smad2 has helped activate transcription, the group previously found, it is shuttled out of the nucleus.

They now discover that this discarded Smad2 is dragged back to the TGF-ß receptor by the microtubule motor kinesin. Smad2 phosphorylation and nuclear accumulation was prevented by microtubule poisons and an antikinesin drug, even in the presence of a constitutively activated receptor. This result held true in frog and zebrafish embryos and mammalian cells. Unphosphorylated Smad2 coimmunoprecipitated with a kinesin light chain.

Long-range transport of Smad2 by kinesin has not yet been demonstrated. Hill also hopes to find a motor that transports active Smad2 from receptor to nucleus. Smad and STAT signaling pathways may be particularly suited to undertake such journeys, as in these two cases a single protein first interacts at the membrane and then acts in the nucleus. In these cases, "I think diffusion is never enough," says Hill. "With cells we tend to assume that things are swimming around in a soup, but I think everything is directed."

Reference:

Batut, J., et al. 2007. Dev. Cell. 12:261–274.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 922K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?